The Structural and Functional Changes Indcuced By Lithium on The Renal Cortex of Growing Albino Rats: Ultrastructure and Laboratory Study.

Introduction: Lithium is a therapeutic agent currently used for the treatment of aff ective disorders controlling a variety of neurotic and psychosomatic manic depressions. Th e main objective of the present work was to demonstrate the histopathological eff ects of the therapeutic doses of Lithium on the renal tubules and glomeruli in growing albino rats. Material and Methods: Th irty growing male Sprague – Dawley albino rats were used in this study. Th e rats were divided into a control group formed of 6 rats and an experimental group formed of 24 rats which received a daily therapeutic dose of 20 mg Lithium/kg body weight by the same route for 7 weeks. Th e renal cortex in all animals is examined by light and electron microscopes. Blood was collected from the sacrifi ced animals for serum creatinine, urea, sodium and potassium to access the eff ect of lithium administration in a therapeutic dose on renal function. Results: Th e present work revealed that the therapeutic doses of Lithium induced nephrotoxicity in the form of degeneration and necrosis in the renal tubules and glomeruli. Alteration in the cellular fi ne structure and degenerated cytoplasm and cytoplasmic organelles were found revealing cellular degeneration and necrosis. Glomerulosclerosis and congestion were the predominant eff ect on the renal glomeruli. Conclusion: Histological and ultrastructrual features of Lithium nephrotoxicity were detected in the current study with therapeutic doses of Lithium.

Papel de las mitocondrias y el estrés oxidativo en el proceso inflamatorio renal / Mitochondria and oxidative stress participation in renal inflammatory process

La muerte celular programada y la fibrosis renal son procesos inherentes a la enfermedad renal crónica y, en tal sentido, ha sido recientemente descripta una clara desregulación de la maquinaria respiratoria mitocondrial en pacientes con enfermedad renal crónica asociada con un aumento del estrés oxidativo. Las células tubulares lesionadas vinculadas a los macrófagos intersticiales y miofibroblastos producen citoquinas y factores de crecimiento que promueven un estado inflamatorio, inducen la apoptosis de las células tubulares y facilitan la acumulación de matriz extracelular. La angiotensina II desempeña un papel central en la fibrogénesis renal y conduce a una rápida progresión de la enfermedad renal crónica. Los niveles crecientes de la angiotensina II inducen citoquinas pro-inflamatorias, la activación de NF-kB, moléculas de adhesión, quimiocinas, factores de crecimiento y estrés oxidativo. Toda la evidencia actual sugiere que la angiotensina II aumenta el estrés oxidativo mitocondrial, regula la inducción de apoptosis y condiciona al estado inflamatorio. Por lo tanto, existiría un papel determinante de las mitocondrias y el estrés oxidativo en el proceso inflamatorio renal. Finalmente, esta revisión resume nuestro actual conocimiento acerca de los posibles mecanismos que contribuirían con la apoptosis modulada por la inflamación y/o el estrés oxidativo durante la enfermedad renal crónica. Además, se propone un nuevo concepto de herramientas anti-inflamatorias que regulan el estrés oxidativo mitocondrial lo cual afectaría directamente al proceso inflamatorio y la apoptosis. Esta idea podría tener consecuencias atractivas sobre el tratamiento de patologías inflamatorias renales y de otras afines.

The apoptosis and renal fibrosis are processes inherent to the chronic kidney disease, and consequently a clear deregulation of the mitochondrial respiratory mechanism has been described in patients with chronic renal disease associated to an increase of the oxidative stress. The injured tubular cells linked to the interstitial macrophages and myofibroblasts produce cytokines and growth factors that encourage an inflammatory condition, inducing the apoptosis of the tubular cells and enabling the accumulation of the extracellular matrix. The angiotensin II has a central role in the renal fibrogenesis leading to a rapid progression of the chronic kidney disease. The growing levels of the angiotensin II induce pro-inflammatory cytokines, the activation of NF-kB, adhesion molecules,chemokines, growth factors, and oxidative stress. The current evidence suggests that the angiotensin II increases the mitochondrial oxidative stress, regulates the induction of the apoptosis and conditions the inflammatory process. Therefore the mitochondria and the oxidative stress would play a determinant role in the renal inflammatory process. Finally, this review summarizes our present knowledge regarding the possible mechanisms that would contribute to the apoptosis conditioned by inflammation and/or oxidative stress during the chronic renal disease. Additionally, a new concept of the anti-inflammatory tools is proposed to regulate the mitochondrial oxidative stress that would directly affect the inflammatory process and apoptosis. This concept could have positive consequences on the treatment of renal inflammatory pathologies and related diseases.

Reduced cortical renal GLUT1 expression induced by angiotensin-converting enzyme inhibition in diabetic spontaneously hypertensive rats

Diabetes in spontaneously hypertensive rats is associated with cortical renal GLUT1 and GLUT2 overexpression. Our objective was to evaluate the effect of the angiotensin-converting enzyme blockade on cortical renal GLUT1 and GLUT2 expression, urinary albumin and urinary TGF-¦Â1. Streptozotocin, 50 mg/kg, or citrate buffer (N = 16) was administered as a single injection into the tail vein in adult spontaneously hypertensive rats (~260 g). Thirty days later, these diabetic spontaneously hypertensive rats received ramipril by gavage: 0.01 mg¡¤kg-1¡¤day-1 (D0.01, N = 14), 1 mg¡¤kg-1¡¤day-1 (D1, N = 9) or water (D, N = 11) for 15 days. Albumin and TGF-¦Â1 (24-h urine), direct arterial pressure, renal tissue angiotensin-converting enzyme activity (fluorometric assay), and GLUT1 and GLUT2 protein levels (Western blot, renal cortex) were determined. Glycemia and glycosuria were higher (P < 0.05) in the diabetic rats compared with controls, but similar between the diabetic groups. Diabetes in spontaneously hypertensive rats lowered renal tissue angiotensin-converting enzyme activity (40 percent), which was reduced further when higher ramipril doses were used. Diabetes associated with hypertension raised GLUT1 by 28 percent (P < 0.0001) and GLUT2 by 76 percent (P = 0.01), and both doses of ramipril equally reduced cortical GLUT1 (D vs D1 and vs D0.01, P ¡Ü 0.001). GLUT2 levels were reduced in D0.01 (P < 0.05 vs D). Diabetes increased urinary albumin and TGF-¦Â1 urinary excretion, but the 15-day ramipril treatment (with either dose) did not reduce them. In conclusion, ramipril is effective in lowering renal tissue angiotensin-converting enzyme activity, as well as blocking cortical GLUT1 overexpression, which may be beneficial in arresting the development of diabetic nephropathy.

Role of nitric oxide and prostaglandin in the maintenance of cortical and renal medullary blood flow

This study was undertaken in anesthetized dogs to evaluate the relative participation of prostaglandins (PGs) and nitric oxide (NO) in the maintenance of total renal blood flow (TRBF), and renal medullary blood flow (RMBF). It was hypothesized that the inhibition of NO should impair cortical and medullary circulation because of the synthesis of this compound in the endothelial cells of these two territories. In contrast, under normal conditions of perfusion pressure PG synthesis is confined to the renal medulla. Hence PG inhibition should predominantly impair the medullary circulation. The initial administration of 25 µM kg-1 min-1 NG-nitro-L-arginine methyl ester produced a significant 26 percent decrease in TRBF and a concomitant 34 percent fall in RMBF, while the subsequent inhibition of PGs with 5 mg/kg meclofenamate further reduced TRBF by 33 percent and RMBF by 89 percent. In contrast, the initial administration of meclofenamate failed to change TRBF, while decreasing RMBF by 49 percent. The subsequent blockade of NO decreased TRBF by 35 percent without further altering RMBF. These results indicate that initial PG synthesis inhibition predominantly alters the medullary circulation, whereas NO inhibition decreases both cortical and medullary flow. This latter change induced by NO renders cortical and RMBF susceptible to a further decrease by PG inhibition. However, the decrease in medullary circulation produced by NO inhibition is not further enhanced by subsequent PG inhibition.

Vitamin A against the acetaminophen- induced toxicity in the renal cortex of albino rats

Acetaminophen [paracetamol; APAP] - induced toxicities have been a major problem in clinical practice. There is no specific treatment for paracetamol poisoning. Vitamin A has shown to have an assisting role in the management of renal inflammatory disorders in animal models as it has anti-inflammatory, antioxidant as well as cytoprotective effect on various renal cell types. To evaluate the possible protective effect of vitamin A against APAP -induced acute renal toxicity in rats. Forty adult male albino rats were used and divided into five groups including control untreated, control vitamin A [12000 IU/kg b.wt, oral], APAP [Ig/kg b.wt, intraperitoneally], APAP+ vitamin A [3000 IU/kg b.wt, oral] and APAP+ vitamin A [12000 IU/kg b.wt, oral]. One week after APAP administration, all rats were anaesthetized. Venous blood was collected; serum and plasma were separated for biochemical assessments. The kidneys were also removed and the renal specimens were submitted to biochemical analysis as well as the microscopic examination using both the light and electron microscopy. Acetaminophen treatment induced increased lipid peroxidation in the plasma and renal tissue. Additionally, increased serum BUN and creatinine levels as well as decreased antioxidant catalase activity were detected indicating a possible involvement of oxidative stress in acetaminophen-induced nephropathy. Microscopic examination revealed massive proximal tubular degeneration, luminal cellular debris associated with partial loss of the luminal brush border. Additionally, cortical interstitial vascular congestion and extravasation of red blood cells were observed. Vitamin A treatment markedly reduced paracetamol- induced renal cortical damage in a dose - dependant manner, as evidenced by the improvement of the biochemical measurements and the marked amelioration of renal pathology. Vitamin A may be a choice of preventive treatment against paracetamol- induced renal damage. The mechanism of protection is probably due to its antioxidant properties and the repairing effect on the damaged tubular cells

Protection against cephalosporin-induced lipid peroxidation and nephrotoxicity by (+)-cyanidanol-3 and vitamin E

The ability of the clinically used cephalosporins: cephalothin, cefotaxime and cefotiam to induce lipid peroxidation (LPO) and renal damage was compared to that of nephrotoxic cephaloridine under in vivo conditions. Glutathione was measured in rat liver or in renal cortex as non-protein sulfhydryls. LPO was measured in plasma, renal cortex and liver by the generation of malondialdehyde or as the increase in renal cortical concentration of conjugated dienes. Impairment of renal function was measured as the decrease in renal cortical accumulation of the organic anion p-aminohippurate (PAH). Administration of cephalosporins to rats as a single dose (2000 mg/kg, ip) induced a significant glutathione-depletion in the renal cortex with cephaloridine, and in the liver with cephaloridine, cephalothin and cefotiam. Treatment of rats with cephaloridine, cephalothin and cefotiam (200, 500, or 1000 mg kg-1 day-1, ip) for 5 days resulted in a dose-dependent increase of LPO in the renal cortex. While cephaloridine induced the highest concentration of conjugated diene, cefotaxime had no effect. Measurements of PAH accumulation in renal cortical slices from cephalosporin-treated rats showed a dose-dependent decrease in the renal cortical accumulation of PAH. Pretreatment with the antioxidants vitamin E or cyanidanol (400 mg kg-1 day-1, ip) 1 h before treatment with cephaloridine, cephalothin or cefotiam (1000 mg kg-1 day-1, ip) for 3 days inhibited cephalosporin-induced LPO and significantly reduced the impairment of renal cortical accumulation of PAH. The potential of different cephalosporins for inducing LPO and reducing PAH accumulation was ranked as follows: cephaloridine > cephalothin > cefotiam > cefotaxime.

Effects of ciprofloxacin on renal cortex of rabbits and the role of vitamin C as a protective agent: anatomical, histological, histochemical and immunohistochemical study

Ciprofloxacin is a fluroquinolone antibiotic commonly used to treat respiratory, urinary tract, skin and soft-tissue infections. The aim of the present work was to study the effects of ciprofloxacin on renal cortex of rabbits and the possible protective role of vitamin C. Twenty four adult male rabbits were used in this study and randomly divided into three groups: control, ciprofloxacin treated and ciprofloxacin plus vitamin C-treated group. This regimen of treatment was given orally for one month. At sacrifice, blood samples were drawn for biochemical study. The kidneys were observed macroscopically and sections were prepared for histological, histochemical and immunohistochemical studies. Ciprofloxacin treated rabbits showed a highly significant increase in Blood urea nitrogen and creatinine. The kidneys of ciprofloxacin treated rabbits appeared small in size with macroscopic evidence of fibrotic capsular thickening. Renal cortex of ciprofloxacin treated rabbits showed moderate tubular dilatation in some proximal and distal convoluted tubules with marked degeneration and vacuolization of their lining cells. Some glomeruli were hypertrophied while others were atrophied. In summary, Ciprofloxacin can induce subtle renal damage which could be ameliorated by simultaneous use of vitamin C which is easily available and safe antioxidant. On the basis of our results, we advice Clinicians to use vitamin C in common with ciprofloxacin to avoid its potential complication

Increased expression of p38 mitogen- activated protein kinase is related to the acute renal lesions induced by gentamicin

Mitogen-activated protein kinases (MAPK) may be involved in the pathogenesis of acute renal failure. This study investigated the expression of p-p38 MAPK and nuclear factor kappa B (NF-kappaB) in the renal cortex of rats treated with gentamicin. Twenty rats were injected with gentamicin, 40 mg/kg, im, twice a day for 9 days, 20 with gentamicin + pyrrolidine dithiocarbamate (PDTC, an NF-kappaB inhibitor), 14 with 0.15 M NaCl, im, twice a day for 9 days, and 14 with 0.15 M NaCl , im, twice a day for 9 days and PDTC, 50 mg kg-1 day-1, ip, twice a day for 15 days. The animals were killed 5 and 30 days after the last of the injections and the kidneys were removed for histological, immunohistochemical and Western blot analysis and for nitrate determination. The results of the immunohistochemical study were evaluated by counting the p-p38 MAPK-positive cells per area of renal cortex measuring 0.05 mm². Creatinine was measured by the Jaffé method in blood samples collected 5 and 30 days after the end of the treatments. Gentamicin-treated rats presented a transitory increase in plasma creatinine levels. In addition, animals killed 5 days after the end of gentamicin treatment presented acute tubular necrosis and increased nitrate levels in the renal cortex. Increased expression of p-p38 MAPK and NF-kappaB was also observed in the kidneys from these animals. The animals killed 30 days after gentamicin treatment showed residual areas of interstitial fibrosis in the renal cortex, although the expression of p-p38 MAPK in their kidneys did not differ from control. Treatment with PDTC reduced the functional and structural changes induced by gentamicin as well as the expression of p-p38 MAPK and NF-kappaB. The increased expression of p-p38 MAPK and NF-kappaB observed in these rats suggests that these signaling molecules may be involved in the pathogenesis of tubulointerstitial nephritis induced by gentamicin.

A low-cost method to test cytotoxic effects of Crotalus vegrandis (Serpentes: Viperidae) venom on kidney cell cultures

La patogénesis de la lesion renal ha sido relacionada a la miolisis, hemólisis, hipotensión y/o el efecto directo del veneno. Tanto el cultivo primario o el cultivo celular continuo proveen una alternativa in vitro para la evaluación cuantitativa de la toxicidad de venenos de serpiente. El veneno crudo de Crotalus vegrandis fue fraccionado por una cromatografía de exclusión molecular. La toxicidad del veneno crudo de C. vegrandis, sus fracciones hemorrágicas y neurotóxicas fueron evaluadas en células renales primarias de ratón y una línea continua de células Vero mantenidas in vitro. Las células fueron aisladas de la corteza renal murina y se cultivaron en placas de 96 pozos con medio Dulbecco (DMEM). Allí fueron tratadas con el veneno crudo y sus fracciones. Las células de la corteza renal murina tuvieron una morfología de células epiteliales y la mayoría se tiñeron con un anticuerpo anti-músculo actina. La citotoxicidad fue evaluada por el método colorimétrico del tetrazolium. La viabilidad de las células fue menor en las células tratadas con el veneno crudo, seguida por la fracción hemorrágica y neurotóxica, con un CT50 de 4.93, 18.41 y 50.22 µg/mL, respectivamente. Los cultivos de células Vero parecieron ser más sensibles con un CT50 de 2.9 y 1.4 µg/mL para el veneno crudo y el pico hemorrágico, respectivamente. Los resultados de este estudio muestran la potencialidad de usar sistemas de cultivo celular para evaluar la toxicidad de los venenos.

Histological and histochemical study of the toxic effect of sodium fluoride and the possible protective role of sodium selenite on the convoluted tubules of the renal cortex of albino rats

Sodium fluaride is known as a specific and effective dental caries rohylactic agent and its systemic or local application is widely recommended in the recent years. It is also used as antihelminthic against roundworms, and for treatment of osteoporosis and otosclerosis in conjunction with calcium supplements and vitamin D. Moreover, it is used for water fluoridation, and as a rodenticide, disinfectant and fungicide. In recent years, acute and chronic toxicity of fluoride has been reported. The purpose of the recent study was to shed light on the histological [light and electron microcopic] and histochemical changes that might occur in the proximal and distal convoluted tubules of the renal cortex of albino rats following acute and chronic sodium fluoride [NaF] toxicity and to investigate the possible protective effect of sodium selenite [Na[2]SeO[3] administration on such toxicity. The present study was carried out on 80 adult male albino rats. They were divided into two main groups: acute NaF toxicity group and chronic NaF toxicity group, each of them included forty rats and was divided equally into four groups which were control group, NaF group, Na[2]SeO[3] group, and NaF and Na[2]SeO[3] group. In the acute toxicity group, NaF group received a single oral dose or NaF [135mg/kg body weight], Na[2]SeO[3] group received a single oral dose of Na[2]SeO[3] [0.35mg/kg body weight/day], while NaF and Na[2]SeO[3] group received a single oral dose of NaF [135mg/kg body weight] simultaneously with a single oral dose of Na[2]SeO[3] [0.35 mg/kg body weigh/day]. On he other hand, in chronic toxicity group, NaF group received NaF orally in a dose of 6mg/kg body weight/day, Na[2]SeO[3] group received Na+2+Se[SeO[3] orally in a dose of 0.35 mg/kg body weight/day, while NaF and Na+2+SeO[3] group received a daily oral dose of NaF [6mg/kg body weight/day] simultaneously with a daily oral dose of Na[2]SeO[3]]0.35mg/kg body weight/day] for three months. All rats were sacrificed 24 hours after their last dosing by decapitation after ether anesthesia Fresh specimens were taken from the renal cortex of each rat and prepared for the histological study [light microscopic examination using haematoxylin and eosin stain, and electron microscopic examination using the transmission electron microscope], and histochemical study [Periodic Acid-Schiff reaction]. The results of the present study revealed that there were marked histological and histochemical changes in the convoluted renal tubules following acute and chronic NaF toxicity. Moreover, sodium selenite was found to be a safe anti-oxidant, when used in appropriate dose, which could offer protection for the renal tissue in chronic NaF toxicity. Hence, it is recommended as a prophylactic agent given to workers highly exposed to sodium fluoride in their work place

Effects of Thyroxine on Hyperkalemia and Renal Cortical Na(+), K(+) - ATPase Activity Induced by Cyclosporin A

Cyclosporin A (CsA)-induced hyperkalemia is caused by alterations in transepithelial K(+) secretion resulting from the inhibition of renal tubular Na(+), K(+) -ATPase activity. Thyroxine enhances renal cortical Na(+), K(+) -ATPase activity. This study investigated the effect of thyroxine on CsA-induced hyperkalemia. Sprague-Dawley rats were treated with either CsA, thyroxine, CsA and thyroxine, or olive-oil vehicle. CsA resulted in an increase in BUN and serum K(+), along with a decrease in creatinine clearance, fractional excretion of potassium, and renal cortical Na(+), K(+) -ATPase activity, as compared with oil vehicle administration. Histochemical study showed reduced Na(+), K(+) -ATPase activity in the proximal tubular epithelial cells of the CsA-treated compared with the oil-treated rats. Histologically, isometric intracytoplasmic vacuolation, disruption of the arrangement and swelling of the mitochondria, and a large number of lysosomes in the tubular epithelium were characteristic of the CsA-treated rats. Co-administration of thyroxine prevented CsA-induced hyperkalemia and reduced creatinine clearance, Na(+), K(+) -ATPase activity, and severity of the histologic changes in the renal tubular cells when compared with the CsA-treated rats. Thyroxine increased the fractional excretion of potassium via the preservation of Na(+), K(+) -ATPase activity in the renal tubular cells. Thus, the beneficial effects of thyroxine may be suited to treatment modalities for CsA-induced hyperkalemia.

Effect of nickel on free radicals production in rat renal cortical mitochondria

In order to elucidate the mechanisms of nickel [Ni+2] induced renal oxidative damage in rats, the ability of renal cortical mitochondria [RCM] to generate reactive oxygen species was investigated in vitro. The generation of superoxide anion radical [O2-] was assessed by the reduction of ferricytochrome c assay. Hydrogen peroxide [H2O2] was monitored by phenol red horseradish peroxidase technique and hydroxyl radicals [OH] generation was monitored by deoxyribose degradation assay in rat RCM incubated with Ni+2. In RCM with or without the addition of Ni+2, catalase, superoxide dismutase [SOD], salicylate, mannitol, phenylalanine, arginine, dimethyl thiourea [DMTU], urea, albumin and desferrioxamine [DFO] were added separately, then incubated at 37C for 90 minutes. The present results indicated that Ni+2 -induced renal oxidative damage is mediated by an accelerated production of reactive oxygen species by RCM

Efectos del paration sobre la actividad de acetilcolinesterasa en rinón de rata

En el presente trabajo se estudió por métodos citoquímicos para microscopía óptica y electrónica, si el paratión (un inhibidos competitivo de acetilcolinesterasa que produce un efecto natriurético), es o no un inhibidor de la enzima a nivel renal, en dois no inhibitorias de AChE de glóbulos rojos (subtóxica). Se utilizaron ratas problema (RP) y ratas controles (RC) con deprivación de agua por 24 horas, inyectadas posteriormente con dosis de paratión intraperitoneal de 600 ug/100g de peso corporal. Para demonstración de actividad de AChE se realizaron incubaciones de riñón por el método de Karnovsky y Roots, variante Tsuji y Larabi. Los resultados de las cinco pruebas de incubación complementarias permiten concluir que existe actividad de AChE en corteza renal y que AChE a nivel renal es inhibida por dosis subtóxicas de paratión intraperitoneal. Se sugiere que el efecto natriurético del paratión se debería a este mecanismo de acción.

Curative effect of methionine on certain enzymes of chick kidney cortex under lanthanum toxicity situation.

Acute single dose administration of lanthanum chloride (250 mg/kg body wt, ip) to chicks have been found to alter the levels of enzymes of the antioxidant defence system of chick renal cortex fractions. Such changes involved significant decrease in activities of glucose-6-phosphate dehydrogenase, glutathione reductase, glutathione peroxidase and catalase of kidney epithelial cells. However glutathione-S-transferase activity was not altered. Glutathione and total thiol contents were decreased while lipoperoxidative reactions in kidney-cortex was significantly enhanced. The data indicate that amelioration of lanthanum toxicity condition by methionine supplementation may be due to the methionine serving as a precursor of glutathione.

Impact of chromium on lipoperoxidative processes and subsequent operation of the glutathione cycle in rat renal system.

Oral administration of K2Cr2O7 to male albino rats at an acute dose of 1500 mg/kg body wt/day for 3 days brought about sharp decrease in the activities of glucose-6-phosphate dehydrogenase and glutathione reductase of kidney epithelial cells. The scavenging system of kidney epithelium is also affected as evident by the highly significant fall in the activities of glutathione peroxidase, superoxide dismutase and catalase which ultimately leads to the increase in lipid peroxidation value in kidney cortical homogenate. However, glutathione-s-transferase activity in cytosol and glutathione and total thiol content in cortical homogenate were not altered. Chronic oral administration of K2Cr2O7 (300 mg/kg body wt/day) for 30 days to rats lead to elevation in the activities of glutathione peroxidase, glutathione reductase, glutathione-s-transferase, superoxide dismutase and catalase with no change in glucose-6-phosphate dehydrogenase activity in epithelial cells. This might lead to the increase in glutathione and total thiol status and decrease in lipid peroxidation value in whole homogenate system.

Studies on human urinary gamma glutamyl transpeptidase

This review discusses the clinical relevance of gamma-GT in urine in health and disease, focusing on the diagnostic usefulness of gamma-GT isoenzymes, as well as current problems in associating gamma-GT molecular heterogenicity and their developments in methodology

Efecto de la Tioacetamida sobre la envoltura nuclear de las células de la corteza renal de la rata / Thioacetamide effects on the nuclear envelope from rat kidney cortex

Se determinó el efecto que produce la administración de Tioacetamida (TAA) sobre la composición y propiedades de los núcleos y envoltura nuclear (EN) purificados de la corteza renal (CR) de ratas, en relación a preparaciones obtenidas de animales controles a través de un método para la obtención de la EN, cuya pureza relativa fue analizada por microscopía electrónica y métodos enzimáticos. En la fracción nuclear de los animales tratados con TAA, se observaron las siguientes alteraciones: aumento en la concentración de RNA y fosfolípidos (pg/Núcleo) en un 77%, un leve incremento de DNA (pg/Núcleo) en un 17%. Por otro lado la concentración de proteínas (pg/Núcleo) permaneció constante. En la EN se encontró que la concentración de DNA disminuyó en un 68% y la de fosfolípidos en un 37%; en cambio la concentración de RNA aumentó discretamente en un 11%. Se encontraron importantes diferencias al estudiar el patrón polipeptídico obtenido al realizar electroforesis en geles de poliacrilamida de EN preparadas a partir de hígado y CR de ratas controles y tratadas con TAA. La actividad específica de la enzima glucosa-6-fosfatasa en los núcleos y EN de los animales tratados con TAA disminuyó en 54% y 43% respectivamente. En los estudios cinéticos se encontró que por efecto de la droga de la Vmax disminuyó significativamente sin alteración del Km. Se discuten las implicaciones de estos resultados